SSRI antidepressants such as Prozac.RTM. (Lilly), Paxil.RTM. (SKB) and Zoloft.RTM. (Pfizer), are characterized by an ability to selectively block reuptake of 5-HT. Selective NE-reuptake inhibitor antidepressants such as Tomoxetine (Lilly) and Vivalan.RTM. (Zeneca) have also been developed (Scheme 1). ##STR1##
Effexor.RTM. and Serzone.RTM. have been termed SNRI antidepressants because they inhibit 5-HT and NE reuptake with similar potency. To achieve an effective therapy for patients for whom present drugs are ineffective, it would be desirable to have drugs which possess reuptake inhibition profiles different from those currently known. Pinder and Wieringa have commented that an agent which simultaneously inhibits reuptake of 5-HT, NE, and DA could be the ultimate reuptake-inhibiting antidepressant drug (Med. Res. Rev., 13, 259-325 (1993)). The present invention provides the first examples of such drugs.